Identification of the role of DAB2 and CXCL8 in uterine spiral artery remodeling in early-onset preeclampsia

Cell Mol Life Sci. 2024 Apr 13;81(1):180. doi: 10.1007/s00018-024-05212-4.ABSTRACTAberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA rem...

Source: Cellular and Molecular Life Sciences : CMLS - April 13, 2024 Category: Cytology Authors: Yu Liu Lili Du Shifeng Gu Jingying Liang Minshan Huang Lijun Huang Siying Lai Shuang Zhang Zhaowei Tu Wei Sun Dunjin Chen Jingsi Chen Source Type: research